Histidine triad nucleotide-binding protein 3 (HINT3)

Histidine triad nucleotide-binding protein 3 is an enzyme in the HIT (histidine triad) superfamily, characterized by the conserved His-ϕ-His-ϕ-His-ϕ-ϕ motif (ϕ = hydrophobic amino acid) near the C-terminus[1][4][6]. HINT3 functions as a nucleotide hydrolase and transferase, acting on the α-phosphate of ribonucleotides and showing preference for acyl-adenylate over nucleoside phosphoramidate substrates[1][4]. The enzyme exists mainly as a monomer and features unique structural elements compared to related family members such as HINT1 and HINT2[1]. Its endogenous substrates and precise physiological roles are still being elucidated, but it is thought to be involved in nucleotide metabolism and cellular response pathways, particularly in the context of cancer cell biology where its expression is regulated by retinoids[4][1][6]. HINT3 has not been implicated as a direct therapeutic target to date, and no inhibitors or drugs are documented to act on this molecule.

Other names

Adenosine 5'-monophosphoramidase HINT3HINT-3FLJ33126HINT4 (note: not synonymous with the distinct HINT4 gene/protein, but sometimes used in older sources)HIT-like protein

Not applicable (no known drugs), but its enzymatic mechanism involves hydrolysis of adenylate intermediates and nucleoside phosphoramidates via a key active-site histidine[4][1].